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Hydrogen sulfide mediates the vasoactivity of garlic

机译:硫化氢介导大蒜的血管活性

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The consumption of garlic is inversely correlated with the progression of cardiovascular disease, although the responsible mechanisms remain unclear. Here we show that human RBCs convert garlic-derived organic polysulfides into hydrogen sulfide (H_2S), an endogenous cardioprotective vascular cell signaling molecule. This H_2S production, measured in real time by a novel polarographic H_2S sensor, is supported by glucose-maintained cytosolic glutathione levels and is to a large extent reliant on reduced thiols in or on the RBC membrane. H_2S production from organic polysulfides is facilitated by allyl sub stituents and by increasing numbers of tethering sulfur atoms. Allyl-substituted polysulfides undergo nucleophilic substitution at the α carbon of the allyl substituent, thereby forming a hydropolysulfide (RS_nH), a key intermediate during the formation of H_2S. Organic polysulfides (R-S_n-R'; n > 2) also undergo nucleophilic substitution at a sulfur atom, yielding RS_nH and H_2S. Intact aorta rings, under physiologically relevant oxygen levels, also metabolize garlic-derived organic polysulfides to liberate H_2S. The vasoactivity of garlic compounds is synchronous with H_2S production, and their potency to mediate relaxation increases with H_2S yield, strongly supporting our hypothesis that H_2S mediates the vasoactivity of garlic. Our results also suggest that the capacity to produce H_2S can be used to standardize garlic dietary supplements.
机译:大蒜的摄入与心血管疾病的发展呈负相关,尽管其作用机理尚不清楚。在这里,我们显示人类红细胞将大蒜衍生的有机多硫化物转化为硫化氢(H_2S),即内源性心脏保护性血管细胞信号分子。由新颖的极谱法H_2S传感器实时测量的H_2S产生得到葡萄糖维持的胞质谷胱甘肽水平的支持,并且在很大程度上依赖于RBC膜中或RBC膜上还原的硫醇。烯丙基取代基和束缚硫原子数目的增加促进了由有机多硫化物生产H_2S。烯丙基取代的多硫化物在烯丙基取代基的α碳上进行亲核取代,从而形成氢多硫化物(RS_nH),这是H_2S形成过程中的关键中间体。有机多硫化物(R-S_n-R'; n> 2)也在硫原子上进行亲核取代,生成RS_nH和H_2S。完整的主动脉环在生理相关的氧气水平下,也会代谢大蒜衍生的有机多硫化物,从而释放出H_2S。大蒜化合物的血管活性与H_2S的产生同步,其介导弛豫的能力随H_2S产量的增加而增加,这有力地支持了H_2S介导大蒜的血管活性的假设。我们的结果还表明,产生H_2S的能力可用于标准化大蒜膳食补充剂。

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